Abstract/Details

NMR, crystallographic and computational investigations of peptides, proteins and bisphosphonates: New paradigms for rational drug design


2008 2008

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Abstract (summary)

The standard approaches to lead identification and optimization involve a long and expensive process including random and nonrandom (targeted or focused) screening. Given the limited success of these standard approaches, an alternate route to develop a new drug would be to start with an existing one. There are many advantages to this strategy since in many cases the "leads" will be in current use in humans or will have been in clinical trials which greatly enhances the likelihood of them being safe for other indications, increasing the probability of eventually obtaining a real drug (as opposed to just an inhibitor). This dissertation explores the potential use of bisphosphonates, a class of molecules currently used clinically in humans for treating bone resorption diseases like osteoporosis, Paget's disease etc, as anti-parasitic, anti-bacterial and anti-cancer agents. The focus of this work can be broadly divided into three areas: (1) using NMR, x-ray crystallography and quantum chemistry to understand protein-ligand interactions, (2) employing computational modeling to gain insights into catalytic mechanisms and evolutionary origins of terpene synthases and cyclases, and finally (3) developing mathematical models based on enzyme-inhibition data and molecular descriptors to predict potency/activity of compounds in cell-based assays.

Indexing (details)


Subject
Pharmacology;
Biophysics
Classification
0419: Pharmacology
0786: Biophysics
Identifier / keyword
Health and environmental sciences; Biological sciences; Bisphosphonates; Cell activity predictions; Computational methods; Drug discovery; Mathematical modeling; NMR; Peptides; Quantum calculations
Title
NMR, crystallographic and computational investigations of peptides, proteins and bisphosphonates: New paradigms for rational drug design
Author
Mukkamala Venkata, C. S. Dushyant
Number of pages
185
Publication year
2008
Degree date
2008
School code
0090
Source
DAI-B 69/11, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549910015
Advisor
Oldfield, Eric
University/institution
University of Illinois at Urbana-Champaign
University location
United States -- Illinois
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3337869
ProQuest document ID
304627234
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/304627234
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